Avycaz

What Is Avycaz?

Avycaz (ceftazidime-avibactam) is an antibacterial combination drug used to treat complicated intra-abdominal infections (cIAI), used in combination with metronidazole; and complicated urinary tract infections (cUTI), including pyelonephritis.

What Are Side Effects of Avycaz?

Common side effects include:

• headache,
• dizziness,
• vomiting,
• nausea,
• abdominal pain,
• diarrhea,
• constipation, and
• anxiety.

Dosage for Avycaz

The recommended dosage of Avycaz is 2.5 grams (2 grams ceftazidime and 0.5 grams avibactam) administered every 8 hours by intravenous (IV) infusion over 2 hours in patients 18 years of age and older. For treatment of cIAI, metronidazole should be given concurrently.

What Drugs, Substances, or Supplements Interact with Avycaz?

Avycaz may interact with probenecid. Tell your doctor all medications and supplements you use.

Avycaz During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before receiving Avycaz. Ceftazidime passes into breast milk. It is unknown if avibactam passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Avycaz (ceftazidime-avibactam) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Avycaz Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe stomach pain, diarrhea that is watery or bloody;
• a seizure (convulsions);
• rigid muscles, overactive reflexes;
• confusion, hallucinations; or
• a change in your mental state.

Common side effects may include:

• nausea, vomiting;
• diarrhea; or
• bruising where the IV needle is placed.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Avycaz (Ceftazidime-avibactam for Injection)

 

Avycaz Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in the Warnings and Precautions section:

• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Clostridium difficile-Associated Diarrhea [see WARNINGS AND PRECAUTIONS]
• Central Nervous System Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience In Adult Patients

AVYCAZ was evaluated in six active-controlled clinical trials in patients with cIAI, cUTI, including pyelonephritis, or HABP/VABP. These trials included two Phase 2 trials, one in cIAI and one in cUTI, as well as four Phase 3 trials, one in cIAI, one in cUTI (Trial 1), one in cIAI or cUTI due to ceftazidime non-susceptible pathogens (Trial 2) and one in HABP/VABP. Data from cUTI Trial 1 served as the primary dataset for AVYCAZ safety findings in cUTI as there was a single comparator. cUTI Trial 2 had an open-label design as well as multiple comparator regimens which prevented pooling, but provided supportive information. The six clinical trials included a total of 1809 adult patients treated with AVYCAZ and 1809 patients treated with comparators.

Complicated Intra-Abdominal Infections

The Phase 3 cIAI trial included 529 adult patients treated with AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered intravenously over 120 minutes every 8 hours plus 0.5 grams metronidazole administered intravenously over 60 minutes every 8 hours and 529 patients treated with meropenem. The median age of patients treated with AVYCAZ was 50 years (range 18 to 90 years) and 22.5% of patients were 65 years of age or older. Patients were predominantly male (62%) and Caucasian (76.6%).

Treatment discontinuation due to an adverse reaction occurred in 2.6% (14/529) of patients receiving AVYCAZ plus metronidazole and 1.3% (7/529) of patients receiving meropenem. There was no specific adverse reaction leading to discontinuation.

Adverse reactions occurring at 5% or greater in patients receiving AVYCAZ plus metronidazole were diarrhea, nausea and vomiting.

Table 11 lists adverse reactions occurring in 1% or more of patients receiving AVYCAZ plus metronidazole and with incidences greater than the comparator in the Phase 3 cIAI clinical trial.

Table 11. Incidence of Selected Adverse Reactions Occurring in 1% or more of Patients Receiving AVYCAZ in the Phase 3 cIAI Trial

Preferred term	AVYCAZ plus metronidazolea (N=529)	Meropenemb (N=529)
Nervous system disorders
Headache	3%	2%
Dizziness	2%	1%
Gastrointestinal disorders
Diarrhea	8%	3%
Nausea	7%	5%
Vomiting	5%	2%
Abdominal Pain	1%	1%
a 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) IV over 120 minutes every 8 hours (with metronidazole 0.5 grams IV every 8 hours) b 1 gram IV over 30 minutes every 8 hours

Increased Mortality

In the Phase 3 cIAI trial, death occurred in 2.5% (13/529) of patients who received AVYCAZ plus metronidazole and in 1.5% (8/529) of patients who received meropenem. Among a subgroup of patients with baseline CrCl 30 to less than or equal to 50 mL/min, death occurred in 19.5% (8/41) of patients who received AVYCAZ plus metronidazole and in 7.0% (3/43) of patients who received meropenem. Within this subgroup, patients treated with AVYCAZ received a 33% lower daily dose than is currently recommended for patients with CrCl 30 to less than or equal to 50 mL/min [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. In patients with normal renal function or mild renal impairment (baseline CrCl greater than 50 mL/min), death occurred in 1.0% (5/485) of patients who received AVYCAZ plus metronidazole and in 1.0% (5/484) of patients who received meropenem. The causes of death varied and contributing factors included progression of underlying infection, baseline pathogens isolated that were unlikely to respond to the study drug, and delayed surgical intervention.

Complicated Urinary Tract Infections, Including Pyelonephritis

The Phase 3 cUTI Trial 1 included 511 adult patients treated with AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered intravenously over 120 minutes every 8 hours and 509 patients treated with doripenem; in some patients parenteral therapy was followed by a switch to an oral antimicrobial agent [see Clinical Studies]. Median age of patients treated with AVYCAZ was 54 years (range 18 to 89 years) and 30.7% of patients were 65 years of age or older. Patients were predominantly female (68.3%) and Caucasian (82.4%). Patients with CrCl less than 30 mL/min were excluded.

There were no deaths in Trial 1. Treatment discontinuation due to adverse reactions occurred in 1.4% (7/511) of patients receiving AVYCAZ and 1.2% (6/509) of patients receiving doripenem. There was no specific adverse reaction leading to discontinuation.

The most common adverse reactions occurring in 3% of cUTI patients treated with AVYCAZ were nausea and diarrhea.

Table 12 lists adverse reactions occurring in 1% or more of patients receiving AVYCAZ and with incidences greater than the comparator in Trial 1.

Table 12. Incidence of Selected Adverse Drug Reactions Occurring in 1% or more of Patients Receiving AVYCAZ in the Phase 3 cUTI Trial 1

Preferred Term	AVYCAZa (N=511)	Doripenemb (N=509)
Gastrointestinal disorders
Nausea	3%	2%
Diarrhea	3%	1%
Constipation	2%	1%
Upper abdominal pain	1%	< 1%
a 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) IV over 120 minutes every 8 hours b 0.5 grams IV over 60 minutes every 8 hours

Hospital-Acquired Bacterial Pneumonia/Ventilator-Associated Bacterial Pneumonia

The Phase 3 HABP/VABP trial included 436 adult patients treated with AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered intravenously over 120 minutes and 434 patients treated with meropenem. The median age of patients treated with AVYCAZ was 66 years (range 18 to 89 years) and 54.1% of patients were 65 years of age or older. Patients were predominantly male (74.5%) and Asian (56.2%).

Death occurred in 9.6% (42/ 436) of patients who received AVYCAZ and in 8.3% (36/434) of patients who received meropenem. Treatment discontinuation due to an adverse reaction occurred in 3.7% (16/436) of patients receiving AVYCAZ and 3% (13/434) of patients receiving meropenem. There was no specific adverse reaction leading to discontinuation.

Adverse reactions occurring at 5% or greater in patients receiving AVYCAZ were diarrhea and vomiting.

Table 13 lists selected adverse reactions occurring in 1% or more of patients receiving AVYCAZ and with incidences greater than the comparator in the Phase 3 HABP/VABP clinical trial.

Table 13. Incidence of Selected Adverse Drug Reactions Occurring in 1% or more of Patients Receiving AVYCAZ in the Phase 3 HABP/VABP Trial

Preferred Term	AVYCAZa (N=436)	Meropenemb (N=434)
Gastrointestinal disorders
Nausea	3%	2%
Skin and subcutaneous tissue disorders
Pruritus	2%	1%
a 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) IV over 120 minutes every 8 hours b 1 gram IV over 30 minutes every 8 hours

Other Adverse Reactions Of AVYCAZ And Ceftazidime In Adults

The following selected adverse reactions were reported in AVYCAZ-treated patients at a rate of less than 1% in the Phase 3 trials and are not described elsewhere in the labeling.

Blood and lymphatic disorders -Thrombocytopenia, Thrombocytosis, Leukopenia

General disorders and administration site conditions -Injection site phlebitis

Infections and infestations -Candidiasis

Investigations -Increased aspartate aminotransferase, Increased alanine aminotransferase, Increased gamma-glutamyltransferase

Metabolism and nutrition disorders -Hypokalemia

Nervous system disorders -Dysgeusia

Renal and urinary disorders -Acute kidney injury, Renal impairment, Nephrolithiasis

Skin and subcutaneous tissue disorders -Rash, Rash maculo-papular, Urticaria

Psychiatric disorders -Anxiety

Additionally, adverse reactions reported with ceftazidime alone that were not reported in AVYCAZ-treated patients in the Phase 3 trials are listed below:

Blood and lymphatic disorders -Agranulocytosis, Hemolytic anemia, Lymphocytosis, Neutropenia, Eosinophilia

General disorders and administration site conditions -Infusion site inflammation, Injection site hematoma, Injection site thrombosis

Hepatobiliary disorders – Jaundice

Investigations -Increased blood lactate dehydrogenase, Prolonged prothrombin time

Nervous system disorders -Paresthesia

Renal and urinary disorders -Tubulointerstitial nephritis

Reproductive and breast disorders -Vaginal inflammation

Skin and subcutaneous tissue disorders -Angioedema, Erythema multiforme, Stevens-Johnson syndrome, Toxic epidermal necrolysis

Laboratory Changes In Adults

In the Phase 3 trials, seroconversion from a negative to a positive direct Coombs’ test result among patients with an initial negative Coombs’ test and at least one follow up test occurred in 3.0% (cUTI), 12.9% (cIAI), and 21.4% (HABP/VABP) of patients receiving AVYCAZ and 0.9% (cUTI), 3% (cIAI) and 7% (HABP/VABP) of patients receiving a carbapenem comparator. No adverse reactions representing hemolytic anemia were reported in any treatment group.

Clinical Trials Experience In Pediatric Patients

AVYCAZ was evaluated in 128 pediatric patients aged 3 months to < 18 years in two single-blind, randomized, active-controlled clinical trials, one in patients with cUTI and the other in patients with cIAI. Safety data from the two studies were pooled. The AVYCAZ dosing regimen was the same in each trial [see DOSAGE AND ADMINISTRATION] with a mean treatment duration of 6 days, and a maximum of 14 days. The regimen was selected to result in pediatric drug exposure comparable to that of adults, and in the cIAI trial, metronidazole was administered concurrently with AVYCAZ. Patients were randomized 3:1 to receive AVYCAZ or comparator, which was meropenem or cefepime in the cIAI and cUTI trials, respectively. The median age of patients treated with AVYCAZ was 8.6 years, and in the comparator group 7.4 years. The majority of patients treated with AVYCAZ were female (57%) and Caucasian (80%).

The safety profile of AVYCAZ in pediatric patients was similar to adults with cIAI and cUTI, treated with AVYCAZ.

There were no deaths reported in either trial. Treatment discontinuation due to adverse reactions occurred in 2.3% (3/128) of patients receiving AVYCAZ and 0/50 of patients receiving comparator drugs.

The most common adverse reactions occurring in greater than 3% of pediatric patients treated with AVYCAZ were vomiting, diarrhea, rash, and infusion site phlebitis.

Read the entire FDA prescribing information for Avycaz (Ceftazidime-avibactam for Injection)